VEGFA and VEGFR2 genetic polymorphisms and survival in patients with diffuse large B cell lymphoma

Abstract

We evaluated the impact of functional polymorphisms in the vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor 2 (VEGFR2) genes on the survival of patients with diffuse large B cell lymphoma (DLBCL). Five potentially functional polymorphisms in the VEGFA (rs699947, rs2010963 and rs3025039) and VEGFR2 (rs1870377 and rs2305948) genes were assessed in 494 DLBCL patients treated with rituximab plus CHOP chemotherapy. The associations of genotype and haplotype with overall survival (OS) and progression-free survival (PFS) were analyzed. Of the five polymorphisms, VEGFR2 rs1870377T>A was significantly associated with both OS and PFS; in the dominant model, patients with the AA + TA genotypes had significantly better OS (P = 0.002) and PFS (P = 0.004) than those with the TT genotype. The association between significantly better OS and the AA + TA genotypes was observed separately in patients with low (0-2; P = 0.035) and high (3-5; P = 0.043) International Prognostic Index scores. Multivariate analysis showed that, relative to the AA + TA genotypes, the TT genotype was an independent prognostic factor for poor OS (HR, 1.71; 95% CI, 1.21-2.43; P = 0.002) and PFS (HR, 1.57; 1.13-2.17; P = 0.004). Other independent significant predictors of survival in patients with DLBCL were International Prognostic Index score, age > 60 years, lactate dehydrogenase concentration >normal, extranodal disease >1 and presence of B symptoms. The VEGFR2 rs1870377 polymorphism might affect survival in patients with DLBCL, suggesting that angiogenesis might be related to poor survival in these patients. (Cancer Sci 2012; 103: 497-503)

Microvessel Density and Expression of Vascular Endothelial Growth Factor and its Receptors in Different Subtypes of Primary Cutaneous B-cell Lymphoma

“…One may speculate that higher VEGF expression in tumour cells of this lymphoma subtype may result from aberrant oncogenic signalling (28). PCLBCL-LT exhibits, among others, an upregulation of bcl-2 and c-myc (2,29).…”

VEGFandbFGFGene Polymorphisms in Patients with Non-Hodgkin's Lymphoma

“…Also bFGF plays an important role in vascular responses by increasing endothelial cell proliferation, stimulating migration, and promoting angiogenesis [19]. Therefore analyses of VEGF and bFGF expressions in haematological malignancies, including NHL, attracted the attention of many researchers [3, 20–22], while there have been fewer studies addressing the role of polymorphic features located within the genes coding for these two angiogenic factors [14, 23, 24] with only two reports describing the association of VEGF genetic polymorphisms with the clinical characteristics of NHL in Asian patients from China [23] and Korea [24]. …”

Preliminary data of VEGF-A and VEGFR-2 polymorphisms as predictive factors of radiological response and clinical outcome in iodine-refractory differentiated thyroid cancer treated with sorafenib

“…SNP genotyping was carried out according to the TaqMan® protocol (Applied biosystems StepOnePlus TM ). Basing on available evidence about functional implications (namely the possible impact on VEGF-A production/ VEGFR-2 ligand affinity) [12,13,[16][17][18] and preceded SNPs association studies addressing the correlation with cancer prognosis [19][20][21][22][23][24][25][26][27], 6 SNPs were selected: −2578 C>A (rs699947), −460 T>C (rs833061), +405 G>C (rs2010963), and +936 C>T (rs3025039) for the VEGF-A gene; +1192 C>T (rs2305948) and +1719 T>A (rs1870377) for the VEGFR-2 gene. Approval by the institutional review board of the University Federico II was obtained.…”